LYSERGIC ACID DIETHYLAMIDE:
An Historical Perspective
By David E. Smith, M.D., M.S.
The ergot alkaloids are a group of drugs obtained from the
fungus ergot, which grows on rye and gives rise to a great
number of medically useful compounds, such as ergonovine and
ergotamine. These latter compounds are used to contract the
uterus after child birth, and for the treatment of migraine
headaches. LSD was first synthesized in 1938 as an
intermediate leading to the synthesis of ergonovine. Its
profound psychological effects were completely unknown at
In 1943, Dr. Albert Hoffman, who was one of the people
involved in the original synthesis, began working with LSD
again. This time he was seeking a stimulant using lysergic
acid (which is the base of all the ergot alkaloids) in
combination with a chemical similar in structure to
nikethamide, a central nervous system stimulant.
One day when he was working with this drug he began to have
some peculiar psychological effects which he described as
"In the afternoon of April 16, 1943, when I was working on
this problem, I was seized by a peculiar sensation of
vertigo and restlessness.
Objects, as well as the shape of my associates in the
laboratory, appeared to undergo optical changes. I was
unable to concentrate on my work. In a dream-like state I
left for home, where an irresistible urge to lie down
overcame me. I drew the curtains and immediately fell into a
peculiar state similar to a drunkenness, characterized by an
"With my eyes closed, fantastic pictures of extraordinary
plasticity and intensive color seemed to surge toward me.
After two hours this state gradually wore off. "
He thought that the psychological effects he had experienced
were due to ingestion of some of the compound he was working
with, and the next day he went back and purposely took what
he considered to be an extremely small dose of the drug, 250
micrograms. (In fact, LSD can exert its psychological
effects in a dose as small as 35 micrograms). He again
developed these unusual psychological effects and, in fact,
found they were now stronger because he apparently had taken
a larger dose the second time.
Physiologically this compound acts as a sympathomimetic
agent. The pupils dilate after taking LSD, the blood
pressure rises slightly, and the pulse quickens. The acute
physiological effects are minor when compared to the
profound psychological effects that occur however, and at
present there is concern over the chronic physiological
toxicity which may take place with repeated LSD ingestion.
Certain clinicians have reported persistent alterations in
E.E.G. patterns in chronic LSD users. These brain wave
changes might suggest chronic brain damage, but at present
there is no documented evidence of brain "organicity" with
LSD. In addition, certain investigators have reported
chromosomal alterations in peripheral white blood cells
secondary to LSD in both in-vitro and in-vivo situations.
There are also isolated reports of teratogenesis in rats
when LSD is injected in the first trimester of pregnancy.
There is no documented proof of human teratogenesis, but it
seems quite clear that LSD is contraindicated in pregnancy
because of its unknown effects on fetal development and
because of its well known uterine stimulant properties.
When someone ingests an average dose of LSD, (150-250
micrograms) nothing happens for the first 30 to 45 minutes,
and then after the sympathetic response the first thing the
individual usually notices are illusions (objects in his
sensory environment changing shape and color. Frequently he
notices that the walls and other objects seem to move. Then
he might notice that colors are looking much brighter or
more intense than they usually appear and, in fact, as time
goes on these colors can seem exquisitely intense and more
beautiful than any colors he has seen before. Also, it is
common for individuals to see a halo around lights, with a
rainbow effect. The ordinary white light looks much
brighter, and one can see numerous colors surrounding it.
Hallucinations, (a false sensory perception without a basis
in external reality) are rather rare with LSD. What is more
common is the phenomena of pseudohallucinations, where the
individual may see something but at the same time he also
knows his perception doesn't have a basis in external
reality. For example, he may see geometric forms of figures
or brilliant colors, but he realizes that they don't really
exist out there.
There is another kind of perceptual change which occurs with
LSD intoxication referred to as a synesthesia. One type of
sensory experience is translated into another, so that if
one is listening to music, for example, one can sometimes
feel the vibrations of the music in one's body, or one can
sometimes see the actual notes moving or the colors that he
is seeing will beat in rhythm with the music so that we have
a translation of one type of sensory experience into another
type of experience.
There is a marked emotional liability and the changes in
emotion are very frequent. Early in the LSD experience, one
is often noted to be euphoric and when the individual is
asked, "Why are you laughing", the person says, "I don't
know, really, but I just feel like laughing." This laughter
can very rapidly change to sadness and crying with very
small changes in the environment. For example, one could be
looking out and seeing green grass and blue sky, and the
green grass looks more green than he has ever seen it
before, and the blue sky is more intense, and he has an
ecstatic feeling over the beautiful colors. Then perhaps the
sun will go behind a cloud, and it gets gray, and suddenly
he feels very blue and very sad, and it seems that
everything in the whole world is turning gray. This is what
is meant by marked emotional lability and the accentuation
Another area where an individual sees changes is the area of
cognitive functioning or value judgment formation. When one
is under the influence of LSD there is no loss of
consciousness. He is fully conscious and usually remembers
most of what happens. Thoughts move much more rapidly than
usual, and one doesn't necessarily think in the same logical
way or on the basis of the standard causal relations. Things
that are ordinarily thought of as being opposite can now
exist together and not appear as opposites.
For example, black and white become equal, or good and bad
frequently become equal. A person can feel heavy and light
at the same time, so there is a breakdown of our ordinary
way of logical thinking; but again if the person is asked to
do something, he usually can perform the task although he
may be annoyed. If you ask him to write his name or take a
psychological test, he may say, "I know I can do this, but
don't bother me now. I just want to go on having my
experience." Time orientation is frequently affected and
past, present and future may merge; special orientation is
also altered and the individual may describe himself as
being" spaced" .
An interesting feature is that anything that happens while
one is under the influence of LSD frequently assumes an
increased sense of meaning and/or increased sense of
importance. When in the LSD state one begins to feel that
certain things which are usually regarded as trivial are now
much more important. For example, when under LSD, one might
look at a rose and feel this is a vision of true beauty, and
the answer to "what is meaningful in life". Unfortunately
such drug-induced insights are transient, but at least
under the influence of LSD, "a rose may be more than a
What the individual experiences while under the influence of
LSD is greatly dependent on his personality structure, his
set or attitude prior to the experience, and the setting or
environment surrounding the drug experience. Variation in
any of these parameters can greatly alter the individual
In the early days after LSD's psychological effects were
discovered it was felt that LSD simulated a model psychosis;
psychological symptoms seen in certain types of psychoses,
such as schizophrenia. Some people expressed the idea that
perhaps this drug could be used as a tool that would induce
a model psychosis, and in this way we could learn more about
schizophrenia and also could perhaps use it as a tool in
drug screening so that if we brought about this model
psychosis with LSD we might then try other drugs which would
reverse the effects and thus have a screen for drugs that
might be useful in treating psychoses.
We no longer think that LSD produces a model psychosis.
While some of the psychological effects it produces are seen
in some forms of mental illness, there are many differences
that are noted. Therefore, most people do not believe that
the model psychosis notion was valid. Along the way people
began searching for endogenous compounds which were like LSD
and which might be responsible for causing illnesses like
schizophrenia, but at the present time no such endogenous
circulating compound has been found.
While the "model psychosis era" of LSD use was slowly losing
momentum, the popular era was just beginning. In 1957, Aldous Huxley wrote "The Doors of Perception" relating his
psychedelic experiences utilizing mescaline, a compound
which has similar psychological properties to LSD. Soon
after, Leary and Alpert, at Harvard, gave birth to the"
psychedelic cult" which included a group of intellectuals in
Cambridge who felt LSD enhanced their powers of creativity.
The media spread the news of the psychedelic cults'
mystical experiences throughout the nation, and today we see
the use of psychedelic chemicals increased by geometrical
proportions, so that in certain subcultures such as the
Haight-Ashbury, use approaches 100%. In later articles the
social significance of such widespread use of powerful
psychedelic chemicals will be discussed.
As to the present medical status of LSD: It is considered an
investigational new drug by the Food and Drug
Administration. That means that there hasn't been
demonstrated for the drug either the requisite safety or
efficacy with regard to its treatment utility to warrant its
being made available on a prescription basis.
At the present time there are a number of studies in
progress to evaluate the usefulness of the drug as a
possible therapeutic agent in the treatment of chronic
alcoholism, psychoneurosis and of autism in children. Some
individuals have also found that in cases of terminal
illness, which some patients have a great difficulty in
accepting, treatment with LSD helps them to accept the
In properly supervised circumstances, with subjects who have
been previously medically and psychiatrically screened, the
incidence of adverse reactions is extremely low. In
circumstances where there is not the proper supervision and
where individuals are not screened before they take the drug
the incidence of adverse effects is significantly higher.
The adverse effects of LSD are largely psychological in nature
and can be divided into acute immediate effects and chronic
First of all, an individual can knowingly take the drug and
then feel that the drug has gotten away from him, and he is
being controlled, or that he can no longer control the
psychological effects that are happening to him. Under this
circumstance some individuals panic and become frightened.
They want to be taken out of this state immediately. They
sometimes try to flee the situation which they are in. At
other times they become quite paranoid and suspicious of
other people who are with them. They begin to feel these
other people are doing something to them or may do something
to them, and they may actually lash out at them. Thus, we
have the acute panic states in which the individual either
tried to flee the situation or actually lashed out.
Secondly, the individuals under LSD can show what, under
ordinary circumstances, we would say is very poor judgment.
For example, they can have the feeling that they are very
light; that they really can fly, and under these
circumstances they can actually go out windows. Individuals
have been reported as walking out into the ocean, feeling
they were" just part of the universe." Individuals have
talked about having a feeling of invincibility, such as,
''It doesn't matter if my body dies; my spirit will live, "
and this mind-body dissociation leads to a variety of
problems, including inadvertent suicide. Following adverse
reactions or "bad trips" a wide variety of long-term
psychological problems can develop.
These chronic psychological after-effects of LSD can be
divided into three categories.
1. The long term schizophrenic reaction: this usually occurs
in people who were disturbed prior to the LSD usage.
2. The long term depression, recurrent panic reactions;
these usually occur in an acute panic reaction.
3. The long term perceptual and recurrent hallucinosis or
In summary: If a person is given LSD under properly
supervised circumstances and is screened medically, the drug
is relatively safe; but when a person who has not been
screened medically and psychiatrically takes LSD of unknown
purity in unknown quantity, in unsupervised circumstances,
it can be an extremely dangerous drug. Unfortunately in the
United States at present, this latter circumstance
predominates and is largely responsible for the high
incidence of adverse reactions to LSD now being seen.